We are investigating optimal procedures for the production of idiotypic immunoglobulin, development of murine monoclonal anti-idiotype antibodies to these immunoglobulins, and evaluating the therapeutic effectiveness of anti-idiotype therapy in patients with B-cell leukemias or lymphomas. It has been possible to produce stable idiotype-secreting heterohybrids by pretreatment of patient tumor cells with 4B-phorbal, 12B-myristate, 13a-acetate (TPA). By growing idiotype-secreting heterohybrids in the peritoneal cavity of nude mice, large quantities of highly concentrated preparations of the patient's idiotypic immunoglobulin have been produced. Anti-idiotype antibodies have been developed for patients with diffuse well-differentiated lymphoma (DWL), chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL). Large amounts of anti-idiotype antibodies are being produced for the treatment of the patients with nodular poorly differentiated lymphoma with a relatively low tumor burden. The goal of current laboratory studies will be to formulate a more efficient technology for the development of anti-idiotype monoclonal antibodies.